rs16924159

Variant names:

• chr9-6229417-G-A
• rs16924159
• NM_033439.4:c.-11-12267G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033439.4(IL33):​c.-11-12267G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,100 control chromosomes in the GnomAD database, including 6,691 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6691 hom., cov: 32)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144
• Publications: 27 publications found

Genes affected

IL33 (HGNC:16028): (interleukin 33) The protein encoded by this gene is a cytokine that binds to the IL1RL1/ST2 receptor. The encoded protein is involved in the maturation of Th2 cells and the activation of mast cells, basophils, eosinophils and natural killer cells. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

ENSG00000294323 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL33	NM_033439.4	c.-11-12267G>A		intron_variant	Intron 1 of 7	ENST00000682010.1	NP_254274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL33	ENST00000682010.1	c.-11-12267G>A		intron_variant	Intron 1 of 7		NM_033439.4	ENSP00000507310.1
IL33	ENST00000417746.6	c.-11-12267G>A		intron_variant	Intron 1 of 4	2		ENSP00000394039.2
ENSG00000294323	ENST00000722750.1	n.187-1122C>T		intron_variant	Intron 2 of 3
ENSG00000294323	ENST00000722751.1	n.232-1122C>T		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42663 AN: 151982 Hom.: 6685 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.299

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.281 AC: 42671 AN: 152100 Hom.: 6691 Cov.: 32 AF XY: 0.284 AC XY: 21100 AN XY: 74332

African (AFR) AF: 0.154 AC: 6403 AN: 41498

American (AMR) AF: 0.348 AC: 5317 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 912 AN: 3470

East Asian (EAS) AF: 0.274 AC: 1416 AN: 5172

South Asian (SAS) AF: 0.358 AC: 1722 AN: 4816

European-Finnish (FIN) AF: 0.315 AC: 3329 AN: 10564

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22558 AN: 67970

Other (OTH) AF: 0.299 AC: 633 AN: 2114

Alfa AF: 0.321 Hom.: 16280

Bravo AF: 0.278

Asia WGS AF: 0.318 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.27
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs16924159; hg19: chr9-6229417; COSMIC: COSV70307198;